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Circadian Variations in Blood Pressure

Implications for Chronotherapeutics

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Abstract

The management of hypertensive patients usually ignores or gives little credit to the biologic rhythms inherent to the disease process and their potential clinical implications. The development of ambulatory blood pressure monitoring and the rapidly growing popularity of home blood pressure measurements by patients have now generated a series of new clinical questions that are directly linked to the chronobiology of the cardiovascular system, such as the clinical interpretation of a blunted nocturnal fall in blood pressure or the difficulty of achieving adequate blood pressure control in the morning. Today, there is growing evidence that night-time blood pressure, and particularly the absence of a decrease in sleep blood pressure, contributes to the occurrence of target organ damages, and that the early morning rise in blood pressure increases the risk of developing cardiovascular events, including stroke, perhaps independently of 24-hour blood pressure levels. On the basis of these observations, it may be necessary to reconsider the way antihypertensive drugs are prescribed in order to obtain smooth, 24-hour blood pressure control, respecting the circadian pattern of blood pressure. Several approaches exist, including the use of drugs that lower blood pressure around the clock and respect the diurnal rhythm. Preliminary studies performed with such agents have provided interesting results. However, there is a clear need for large clinical trials demonstrating the clinical superiority of this approach. In any case, a better understanding of the importance of the circadian variations of blood pressure could certainly have a major impact on our view of the therapeutic management of hypertensive patients.

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References

  1. MacMahon S, Peto R, Culer J, et al. Blood pressure, stroke, and coronary heart disease: part 1. Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 1990; 335: 765–74

    Article  PubMed  CAS  Google Scholar 

  2. Mancia G, Carugo S, Grassi G, et al. Prevalence of left ventricular hypertrophy in hypertensive patients without and with blood pressure control. Hypertension 2002; 39: 744–9

    Article  PubMed  CAS  Google Scholar 

  3. Maocia G, Sega R, Milesi C, et al. Blood-pressure control in the hypertensive population. Lancet 1997; 349(9050): 454–7

    Article  Google Scholar 

  4. Burt VL, Cutler JA, Higgins M, et al. Trends in the prevalence, awareness, treatment, and control of hypertension in the adult US population: data from the Health Examination Surveys, 1960 to 1991. Hypertension 1995; 26: 60–9

    Article  PubMed  CAS  Google Scholar 

  5. Appel LT, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. N Engl J Med 1997; 336: 1117–24

    Article  PubMed  CAS  Google Scholar 

  6. Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet: DASH-sodium Collaborative Research Group. N Engl J Med 2001; 344(1): 3–10

    Article  PubMed  CAS  Google Scholar 

  7. Guidelines Committee. 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21(6): 1011–53

    Article  Google Scholar 

  8. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289: 2560–72

    Article  PubMed  CAS  Google Scholar 

  9. Brunner HR, Ménard J, Waeber B, et al. Treating the individual hypertensive patient: considerations on dose, sequential monotherapy and drug combinations. J Hypertens 1990; 8: 3–11

    Article  PubMed  CAS  Google Scholar 

  10. Dickerson JE, Hingorani AD, Ashby MJ, et al. Optimisation of antihypertensive treatment by crossover rotation of four major classes. Lancet 1999; 353(9169): 2008–13

    Article  PubMed  CAS  Google Scholar 

  11. Fenickel RR, Lipicky RJ. Combination products as first-line pharmacotberapy. Arch Intern Med 1994; 154: 1429–30

    Article  Google Scholar 

  12. Waeber B, Brunner HR. Combination antihypertensive therapy: does it have a role in rational therapy? Am J Hypertens 1997; 10 (7 Pt 2): 131S–7S

    Article  PubMed  CAS  Google Scholar 

  13. Smolensky MH, Haus E. Orcadian rhythms and clinical medicine with applications to hypertension. Am J Hypertens 2001; 14: 280S–90S

    Article  PubMed  CAS  Google Scholar 

  14. Staessen J, Bulpitt CJ, O’Brien E, et al. The diurnal blood pressure profile: a population study. Am J Hypertens 1992; 5: 386–92

    PubMed  CAS  Google Scholar 

  15. Pickering TG. Diurnal rhythms and other sources of blood pressure variability in normal and hypertensive subjects. In: Laragh J, Brenner BM, editors. Hypertension: pathopbysiology, diagnosis and management. Vol. I. New York: Raven, 1990: 1397–405

    Google Scholar 

  16. Portaluppi F, Smolenski MH. Time-dependent structure and control of arterial blood pressure. Ann N Y Acad Sci 1996; 783: 1–342

    Article  PubMed  CAS  Google Scholar 

  17. Baumgart P. Circadian rhythm of blood pressure: internal and external time triggers. Chronobiol Int 1991; 8: 444–50

    Article  PubMed  CAS  Google Scholar 

  18. Sternberg H, Rosenthal T, Shamiss A, et al. Altered circadian rhythm of blood pressure in shift workers. J Hum Hypertens 1995; 9: 349–53

    PubMed  CAS  Google Scholar 

  19. Omboni S, Parati G, Palatini P, et al. Reproducibility and clinical value of nocturnal hypotension: prospective evidence from the SAMPLE study. J Hypertension 1998; 16: 733–8

    Article  CAS  Google Scholar 

  20. Manning G, Rushton L, Donnelly R, et al. Variability of diurnal changes in ambulatory blood pressure and nocturnal dipping status in untreated hypertensive and normotensive subjects. Am J Hypertens 2000; 13(9): 1035–8

    Article  PubMed  CAS  Google Scholar 

  21. Uzu T, Fujii T, Nisbimura M, et al. Determinants of circadian blood pressure rbythm in essential hypertension. Am J Hypertens 1999; 12 (1 Pt 1): 35–9

    Article  PubMed  CAS  Google Scholar 

  22. Fujii T, Uzu T, Nishimura M, et al. Circadian rhythm of natriuresis is disturbed in nondipper type of essential hypertension. Am J Kidney Dis 1999; 33(1): 29–35

    Article  PubMed  CAS  Google Scholar 

  23. Uzu T, Kimura G. Diuretics shift circadian rhythm of blood pressure from nondipper to dipper in essential hypertension. Circulation 1999; 100(15): 1635–8

    Article  PubMed  CAS  Google Scholar 

  24. Bankir L, Sellin F, Chiolero A, et al. A reduced nocturnal dipping in blood pressure in patients with moderate essential hypertension is associated with a disturbed diurnal/nocturnal pattern of water and sodium excretion [abstract]. J Am Soc Nephrol 2003; 14: 20A

    Google Scholar 

  25. Willich SN, Levy D, Rocco MB, et al. Circadian variation in the incidence of sudden cardiac death in the Framingham Heart Study population. Am J Cardiol 1987; 60: 801–6

    Article  PubMed  CAS  Google Scholar 

  26. Marler JR, Price TR, Clark GL., et al. Morning increase in onset of ischemic stroke. Stroke 1989; 20: 473–6

    Article  PubMed  CAS  Google Scholar 

  27. Argentine C, Toni D, Rasura M, et al. Circadian variation in the frequency of ischemie stroke. Stroke 1990; 12: 387–9

    Article  Google Scholar 

  28. Muller JE, Stone PH, Turi ZG, et al. Circadian variation in the frequency of onset of acute myocardial infarction. N Engl J Med 1985; 313: 1315–22

    Article  PubMed  CAS  Google Scholar 

  29. Mulcahy D, Keegan J, Cunningham D, et al. Circadian variation of total ischemic burden and its alteration with antianginal agents. Lancet 1988; II: 755–9

    Article  Google Scholar 

  30. Muller JE, Toffler GH, Stone PLI. Circadian variation and triggers of onset of acute cardiovascular disease. Circulation 1989; 79: 733–43

    Article  PubMed  CAS  Google Scholar 

  31. Verdecchia P, Porcellati C, Schillaci G. Ambulatory blood pressure: an independent predictor of prognosis in essential hypertension. Hypertension 1994; 24: 793–801

    Article  PubMed  CAS  Google Scholar 

  32. Ferrara AL, Pasanisi F, Crivaro M, et al. Cardiovascular abnormalities in nevertreated hypertensives according to nondipper status. Am J Hypertens 1998; 11 (11 Pt 1): 1352–7

    Article  PubMed  CAS  Google Scholar 

  33. Mancia G, Parati G. Ambulatory blood pressure monitoring and organ damage. Hypertension 2000; 36: 894–900

    Article  PubMed  CAS  Google Scholar 

  34. Kario K, Pickering TG, Matsuo T, et al. Stroke prognosis and abnormal nocturnal blood pressure falls in older hypertensives. Hypertension 2001; 38: 852–7

    Article  PubMed  CAS  Google Scholar 

  35. Cuspidi C, Lonati L, Sampieri L, et al. Impact of nocturnal fall in blood pressure on early cardiovascular changes in essential hypertension. J Hypertens 1999; 17: 1339–44

    Article  PubMed  CAS  Google Scholar 

  36. Nishimura M, Uzu T, Fujii T, et al. Disturbed circadian rhythm of urinary albumin excretion in non-dipper type of essential hypertension. Am J Nephrol 2002; 22(5–6): 455–62

    Article  PubMed  Google Scholar 

  37. Lurbe E, Redon J, Kesani A, et al. Increase in nocturnal blood pressure and progression to microalbuminuria in type 1 diabetes. N Engl J Med 2002; 347(11): 797–805

    Article  PubMed  CAS  Google Scholar 

  38. Ohkubo T, Hozawa A, Nagai K, et al. Prediction of stroke by ambulatory blood pressure monitoring versus screening blood pressure measurements in a general population: the Ohasama study. J Hypertens 2000; 18(7): 847–54

    Article  PubMed  CAS  Google Scholar 

  39. Imai Y, Tsuji I, Nagai K, et al. Circadian blood pressure variation related to morbidity and mortality from cerebrovascular and cardiovascular diseases. Ann N Y Acad Sci 1996 Aug 15; 783: 172–85

    Article  PubMed  CAS  Google Scholar 

  40. Björklund K, Lind L, Andren B, et al. The majority of nondipping men do not have increased cardiovascular risk: a population based study. J Hyperteus 2002; 20: 1501–6

    Article  Google Scholar 

  41. Morgan TO, Anderson A. Different drug classes have variable effects on blood pressure depending on the time of the day. Am J Hypertens 2003; 16: 46–50

    Article  PubMed  CAS  Google Scholar 

  42. Perloff D, Sokolow D, Cowan R. The prognostic value of ambulatory blood pressure. JAMA 1983; 249: 2793–8

    Article  Google Scholar 

  43. Ohkubo T, Imai Y, Tsuji I, et al. Prediction of mortality by ambulatory blood pressure monitoring versus screening blood pressure measurements: a pilot study in Ohasama. J Hypertens 1997; 15: 357–64

    Article  PubMed  CAS  Google Scholar 

  44. Mancia G, Zanchetti A, Agabiti-Rosei E, et al. Ambulatory blood pressure is superior to clinic blood pressure in predicting treatment-induced regression of left-ventricular hypertrophy: SAMPLE study group. Circulation 1997; 95: 1464–70

    Article  PubMed  CAS  Google Scholar 

  45. Redon J, Campos C, Narciso ML, et al. Prognostic value of ambulatory blood pressure monitoring in refractory hypertension: a prospective study. Hypertension 1998; 31: 712–8

    Article  PubMed  CAS  Google Scholar 

  46. Zanchetti A, Bond MG, Hennig M, et al. Risk factors associated with alterations in carotid intima-media thickness in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis. The ELSA Study Group. J Hypertens 1998; 16: 949–61

    Article  PubMed  CAS  Google Scholar 

  47. Neutel JM, Smith DHG. Chronotherapeutics in the treatment of hypertension. In: Oparil S, Weber M, editors. Hypertension: a companion to Brenner and Rector’s The kidney. St Louis (PA): W.B. Saunders, 2000: 504–8

    Google Scholar 

  48. Harshfield GA, Hwang C, Grim CE. Circadian variation in blood pressure in blacks: influence of age, gender and activity. J Hum Hypertens 1990; 4(1): 43–7

    PubMed  CAS  Google Scholar 

  49. Kario K, Pickering TG, Umeda Y, et al. Morning surge in blood pressure as a predictor of silent and clinical cerebrovascular disease in elderly hypertensives: a prospective study. Circulation 2003; 107: 1401–6

    Article  PubMed  Google Scholar 

  50. Clement DL, De Buyzere ML, De Bacquer DA, et al. Prognostic value of ambulatory blood pressure recordings in patients with treated hypertension. N Engl J Med 2003; 348: 2407–15

    Article  PubMed  Google Scholar 

  51. Morgan T, Brunner HR, Aubert JF, et al. The relationship of blood pressure to cardiac hypertrophy: experimental studies in rats. Clin Exp Hypertens 1997; 19: 827–41

    Article  PubMed  CAS  Google Scholar 

  52. Morgan T, Brunner HR, Aubert JF, et al. Cardiac hypertrophy depends upon sleep blood pressure: a study in rats. J Hypertens 2000; 18: 445–51

    Article  PubMed  CAS  Google Scholar 

  53. Pecbére-Bertschi A, Nussberger J, Decosterd L, et al. Renal response to the angiotensin II receptor subtype 1 irbesartan versus enalapril in hypertensive patients. J Hypertens 1998; 16: 385–93

    Article  Google Scholar 

  54. Forclaz A, Maillard M, Nussberger J, et al. Angiotensin II receptor blockade: is there truly a benefit of adding an ACE inhibitor? Hypertension 2003; 41: 31–6

    Article  PubMed  CAS  Google Scholar 

  55. McIntyre M, Caffe SE, Michalak RA, et al. Losartan, an orally active angiotensin (AT1) receptor antagonist: a review of its efficacy and safety in essential hypertension. Pharmacol Ther 1997; 74(2): 181–94

    Article  PubMed  CAS  Google Scholar 

  56. Neutel J, Smith DH. Evaluation of angiotensin II receptor blockers for 24-hour blood pressure control: meta-analysis of a clinical database. J Clin Hypertens 2003; 5(1): 58–63

    Article  CAS  Google Scholar 

  57. Pitt B, Poole-Wilson PA, Segal R, et al. Effect of losartan compared with Captopril on mortality in patients with symptomatic heart failure: randomised trial: the Losartan Heart Failure Survival Study ELITE II. Lancet 2000; 355: 1582–7

    Article  PubMed  CAS  Google Scholar 

  58. Dickstein K, Kjekshus J. Effects of losartan and Captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal Trial In Myocardial Infarction with Angiotensin II Antagonist Losartan. Lancet 2002; 360: 752–60

    Article  PubMed  CAS  Google Scholar 

  59. Dahlöf B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet 2002; 359: 995–1003

    Article  PubMed  Google Scholar 

  60. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345: 861–9

    Article  PubMed  CAS  Google Scholar 

  61. Poirier L, Lefebvre J, Lacourciére Y. Chronotherapeutics: are there meaningful differences among antihypertensive drugs? Curr Hypertens Rep 1999; 1: 320–7

    Article  PubMed  CAS  Google Scholar 

  62. Morgan TO, Anderson A, Jones E. The effect on 24-hour blood pressure control of an angiotensin converting enzyme inhibitor (Perindopril) administered in the morning or at night. J Hypertens 1997; 15: 205–11

    Article  PubMed  CAS  Google Scholar 

  63. Palatini P, Racioppa A, Raule G, et al. Effect of timing of administration on the plasma ACE inhibitor activity and the antihypertensive effect of quinapril. Clin Pharmacol Ther 1992; 52: 378–83

    Article  PubMed  CAS  Google Scholar 

  64. Anwar YA, White WB. Chronotherapeutics for cardiovascular disease. Drugs 1998; 55: 631–43

    Article  PubMed  CAS  Google Scholar 

  65. Brandenburger G, Follenius M, Goichot B, et al. Twenty-four hour profiles of plasma renin activity in relation to the sleep-wake cycle. J Hypertens 1994; 12: 277–83

    Google Scholar 

  66. Kario K, Matsuo T, Kobayashi H, et al. Nocturnal fall of blood pressure and silent cerebrovascular damage in elderly hypertensive patients: advanced silent cerebrovascular damage in extreme dippers. Hypertension 1996; 27: 130–5

    Article  PubMed  CAS  Google Scholar 

  67. Würzner G, Gerster JC, Chiolero A, et al. Comparative effects of losartan and irbesartan on serum acid in hypertensive patients with hyperuricemia and gout. J Hypertension 2001; 19: 1855–60

    Article  Google Scholar 

  68. Mancia G, Cattaneo BM, Omboni S, et al. Clinical benefits of a consistent reduction in blood pressure. J Hypertens Suppl 1998; 16: S35–9

    PubMed  CAS  Google Scholar 

  69. Parati G, Omboni S, Rizzoni D, et al. The smoothness index: a new, reproducible and clinically relevant measure of the homogeneity of the blood pressure reduction with treatment of hypertension. J Hypertens 1998; 16: 1685–91

    Article  PubMed  CAS  Google Scholar 

  70. Prisant LM, Black HR, Messerli F, et al. Chrono: a community-based hypertension trial of a chronotherapeutic formulation of Verapamil. Am J Ther 2002; 9(6): 476–83

    Article  PubMed  Google Scholar 

  71. Kang D, Verotta D, Krecic-Shepard ME, et al. Population analyses of sustainedrelease Verapamil in patients: effects of sex, race, and smoking. Clin Pharmacol Ther 2003; 73(1): 31–40

    Article  PubMed  CAS  Google Scholar 

  72. White WB, LaRocca GM. Chronopharmacology of cardiovascular therapy. Blood Press Monit 2002; 7(4): 199–207

    Article  PubMed  Google Scholar 

  73. White WB, Sica DA, Calhoun D, et al. Preventing increases in early-morning blood pressure, heart rate, and the rate-pressure product with controlled onset extended release Verapamil at bedtime versus enalapril, losartan, and placebo on arising. Am Heart J 2002; 144(4): 657–65

    PubMed  CAS  Google Scholar 

  74. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients: the Heart Outcomes Prevention Evaluation study investigators. N Engl J Med 2000; 342: 145–53

    Article  PubMed  CAS  Google Scholar 

  75. Svensson P, DeFaire U, Sleight P, et al. Comparative effects of ramipril on ambulatory and office blood pressures: a HOPF, substudy. Hypertension 2001; 38: E28–32

    Article  PubMed  CAS  Google Scholar 

  76. Mancia G, Omboni S, Parati G, et al. Twenty-four hour ambulatory blood pressure in the Hypertension Optimal Treatment (HOT) study. J Hypertens 2001; 19(10): 1755–63

    Article  PubMed  CAS  Google Scholar 

  77. Mancia G, Omboni S, Parati G, et al. Twenty-four hour ambulatory blood pressure in the International Nifedipine GITS Study Intervention as a Goal in Hypertension Treatment (INSIGHT). J Hypertens 2002; 20(3): 545–53

    Article  PubMed  CAS  Google Scholar 

  78. Lacourciere Y, Lenis J, Orchard R, et al. A comparison of the efficacies and duration of action of the angiotensin II receptor blockers telmisartan and amlodipine. Blood Press Monit 1998; 3(5): 295–302

    PubMed  Google Scholar 

  79. Black HR, Elliott WJ, Grandits G, et al. Principal results of the controlled onset Verapamil investigation of cardiovascular end point (CONVINCE) trial. JAMA 2003; 289: 2073–82

    Article  PubMed  CAS  Google Scholar 

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Hassler, C., Burnier, M. Circadian Variations in Blood Pressure. Am J Cardiovasc Drugs 5, 7–15 (2005). https://doi.org/10.2165/00129784-200505010-00002

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